In heart failure, a functional block of complex I of the respiratory chain provokes superoxide generation, which is transformed to H2O2 by dismutation. The Krebs cycle produces NADH, which delivers electrons to complex I, and NADPH for H2O2 elimination via isocitrate dehydrogenase and nicotinamide nucleotide transhydrogenase (NNT). At high NADH levels, α-ketoglutarate dehydrogenase (α-KGDH) is a major source of superoxide in skeletal muscle mitochondria with low NNT activity. Here, we analyzed how α-KGDH and NNT control H2O2 emission in cardiac mitochondria. In cardiac mitochondria from NNT-competent BL/6N mice, H2O2 emission is equally low with pyruvate/malate (P/M) or α-ketoglutarate (α-KG) as substrates. Complex I inhibition with rotenone increases H2O2 emission from P/M, but not α-KG respiring mitochondria, which is potentiated by depleting H2O2-eliminating capacity. Conversely, in NNT-deficient BL/6J mitochondria, H2O2 emission is higher with α-KG than with P/M as substrate, and further potentiated by complex I blockade. Prior depletion of H2O2-eliminating capacity increases H2O2 emission from P/M, but not α-KG respiring mitochondria. In cardiac myocytes, downregulation of α-KGDH activity impaired dynamic mitochondrial redox adaptation during workload transitions, without increasing H2O2 emission. In conclusion, NADH from α-KGDH selectively shuttles to NNT for NADPH formation rather than to complex I of the respiratory chain for ATP production. Therefore, α-KGDH plays a key role for H2O2 elimination, but is not a relevant source of superoxide in heart. In heart failure, α-KGDH/NNT-dependent NADPH formation ameliorates oxidative stress imposed by complex I blockade. Downregulation of α-KGDH may, therefore, predispose to oxidative stress in heart failure.To characterize dietary patterns and physical activity in a diverse cohort of Midwestern reproductive-age women and to determine associations between these lifestyle factors, socioeconomic factors, and obesity.
In this cross-sectional study, 185 women completed validated food frequency and physical activity questionnaires. Dietary patterns were identified through principal component analysis. Sociodemographic characteristics associated with dietary pattern adherence and physical activity participation were identified through linear regression. Associations between lifestyle factors and obesity were assessed through logistic regression.
Two dietary patterns were identified a "Prudent" pattern characterized by consumption of fruits, vegetables, olive oil, and nuts and a "Western" pattern including meat, refined carbohydrates, and high-calorie drinks. https://www.selleckchem.com/ African-American women and women without a college degree were more likely to adhere to the Western dietary pattern than other women. Women in areas with hig interventions focused on minimizing consumption of the Western diet and increasing physical activity may provide an opportunity to reduce obesity among reproductive-age women.With funding from the Pregnancy Assistance Fund, the Maternal, Child, and Adolescent Health Division (MCAH) of California redesigned its existing Adolescent Family Life Program (AFLP) for expectant and parenting young women into a more intensive and structured intervention, AFLP with positive youth development (PYD). This paper presents key findings from a federally funded, rigorous implementation study of the two programs.
This implementation study collected data from 13 agencies from January 2016 through December 2017, including interviews with 69 case managers and 18 supervisors; focus groups with 130 program participants; surveys of 66 case managers and 1330 young women; and observations of 42 visits with program participants. The study combined qualitative and quantitative analysis methods.
As designed, PYD was a much more structured and intensive program than AFLP. Case managers and supervisors saw value in the PYD model and new approach but needed more support and guidance than expected in order in implementation and providing more detailed preservice training to prepare staff for real-world implementation.Cardiac troponin (cTn) is the biomarker of choice for the diagnosis of acute myocardial infarction (MI); use of this biomarker has centered around the 99th percentile upper reference limit (URL) for healthy populations. Recent development and regulatory approval of high-sensitivity cardiac troponin (hs-cTn) assays have required a fresh look at utilization of the 99th percentile URL. This review covers issues regarding the 99th percentile URL and approaches for use of cTn as biomarker for detecting cardiac injury and diagnosis of acute myocardial infarction.
Development of hs-cTn assays has allowed determination and use of sex-specific 99th percentile URLs for assessing cardiac injury and increased the utility of cTn values below the 99th percentile URL. This improved analytical performance for hs-cTn assays has allowed for development of accelerated diagnostic protocols (ADPs) for rapid assessment and disposition of patients based on serial sampling of cTn for use in acute MI diagnosis as soon as 0-1h aftile URLs in the era of hs-cTn results may be modified. ADPs have the potential to substantially decrease the time many patients spend under evaluation for acute MI, thereby potentiating improvement in patient satisfaction, decreased healthcare costs, and reducing the burden on emergency departments.Stress is a major risk factor for bipolar disorder. Even though we do not completely understand how stress increases the risk for the onset and poorer course of bipolar disorder, knowledge of stress physiology is rapidly evolving. Following stress, stress hormones - including (nor)adrenaline and corticosteroid - reach the brain and change neuronal function in a time-, region-, and receptor-dependent manner. Stress has direct consequences for a range of cognitive functions which are time-dependent. Directly after stress, emotional processing is increased at the cost of higher brain functions. In the aftermath of stress, the reverse is seen, i.e., increased executive function and contextualization of information. In bipolar disorder, basal corticosteroid levels (under non-stressed conditions) are generally found to be increased with blunted responses in response to experimental stress. Moreover, patients who have bipolar disorder generally show impaired brain function, including reward processing. There is some evidence for a causal role of (dysfunction of) the stress system in the etiology of bipolar disorder and their effects on brain system functionality.